dr andrew dodgson consultant microbiologist and infection control doctor
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Carbapenemases in practice - lessons learnt from spread in our patch, prophylaxis and first/second line treatments. Dr Andrew Dodgson Consultant Microbiologist and Infection Control Doctor Health Protection Agency & Central Manchester University Hospitals NHS Foundation Trust. Carbapenemases. - PowerPoint PPT PresentationTRANSCRIPT
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Carbapenemases in practice - lessons learnt from spread in our patch, prophylaxis and
first/second line treatments
Dr Andrew DodgsonConsultant Microbiologist and Infection Control Doctor
Health Protection Agency & Central Manchester University Hospitals NHS Foundation Trust
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Carbapenemases
• Phenotypically similar enzymes
• Genotypically diverse
• Epidemiologically Diverse
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Classification
• Class A (serine based)• KPC, GES, SME, NMC, IMI
• Class B (metallo-enzymes)• NDM, IMP, VIM, GIM, SIM, SMP, L1, BCII, Ccra
• Class D (serine)• OXA
From Queenan and Bush, CMR 2007
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Classification
• Chromosomal– Class A• SME, NMC, IMI
– Class B• BCII, L1, Ccra
• Plasmid– Class A• KPC, GES
– Class B• NDM, IMP
– Class D• OXA
From Queenan and Bush, CMR 2007
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“Transmission” of Resistance
• Clonal spread (particularly ST258 K. pneumo for KPC)
• Transmission of plasmid
• Other enterobacteriaceae implicated, e.g. Enterobacter, E.coli
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Therapy
• Need to know local epidemiology
• i.e. clonal spread– all isolates have the same antibiogram
• or polyclonal, transmission of plasmid– sensitivities vary depending on the background of
the strain carrying the plasmid
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Local situation?
• Many different strains• Same plasmid
Enterobacter
E. coli
KPC producer from a nearby hospital
Courtesy N. Woodford
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Carbapenems?
• Some carbapenemase producers will have MIC’s below the breakpoint for resistance
Carmeli et al. CMI 2010
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S I R
Erta ≤0.5 1 >1
0.5->64
Imi ≤2 4-8 >8
0.5->64
Mero ≤2 4-8 >8
1-64
Miriagou et al. CMI 2010.
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Carbapenems?
• Some carbapenemase producers will have MIC’s below the breakpoint for resistance
• Carbapenems show some activity in animal models against these strains
• Strong inoculum effect noted in in-vitro models
• MIC ≤8 Mortality 29%, MIC>8 75%
Carmeli et al. CMI 2010; Daikos et al, AAC 2009
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Other options
• Again, depends on susceptibility results.• Many strains multi (or almost pan-) resistant
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Other options– Quinolones– Aminoglycosides– Tigecycline– Colistin– Trimethoprim– Fosfomycin– Temocillin– Combinations (which ones?)
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What should we do?
• Review of 298 published cases (244 BSI)
Tzouvelekis et al, CMR 2011
Treatment Failure rate2 drugs, inc carbapenem (MIC<8) 8%
2 drugs, no carbapenem 29%
Aminoglycoside alone 24%
Carbapenem alone(MIC<8) 25%
Tigecycline alone 36%
Colistin alone 47%
Inappropriate Rx 54%
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Sensitivities
• Data from 30 Blood culturesSensitive (%) Intermediate( %) Resistant (%)
Colistin 92 8
Amikacin 77 10 13
Tigecycline 74 13 13
Gentamicin 58 3 39
Temocillin 57 43
Ciprofloxacin 52 48
Trimethoprim 48 52
Meropenem 3 10 87
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What do we do?
• Plasmid mediated resistance• Necessitates individual patient approach• Usually based on sensitivities of previous
screening or clinical isolates• Some broad principles:– 2 agents – B-lactam (if poss) – Aminoglycoside if possible – Colistin never alone
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Prophylaxis
• Difficult to generalise due to variable susceptibilities– GI Surgery• Tigecycline
– Urology• Aminoglycoside or Cipro
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Empiric Rx
• Paeds neutropenic sepsis:– Pip/Taz and Amikacin 1st line– Close scrutiny of sens of all BC’s– And sens of CPC screening isolates – No Amik resistance (yet)
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Empiric Rx
• GNR in blood culture, pt known to be colonised
• Depends on sens and site of primary infection• Toxicity often less of a concern (due to lack of
options)• Almost always add suitable aminoglycoside• Tige/Colistin not used alone
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Empiric Rx
• What have we done?– 30 bacteraemic adult pt’s– 18 different regimes used– 11 received monotherapy (cip 4, gent 4, tige, col,
mero)– 15 had 2 Abx, 1 had 3 and 1 4.– 16 of 19 with 2 or more abx had an aminoglycoside
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Summary
• Carbapenemase producing enterobacteriaceae are heterogenous
• Know your local epidemiology• Take MIC’s into account (esp. Carb’s)• Be prepared to think laterally
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Acknowledgements
• Dr Louise Sweeney• Dr Barry Neish• All the Micro staff at CMFT• Prof Neil Woodford